Aggressive treatment for head and neck cancer (HNC) has improved survival rates. This improvement comes with a marked increase in acute and late-effects of treatment. [Late-effects may be secondary to treatment] (surgery, radiation, and chemotherapy) or effects of the tumor itself. They have a profound impact on [survivor's long-term symptom burden, functionality, and overall quality of life (QOL). Under- standing the mechanisms and manifestations of late-effects is critical to the design of interventions for improvement of quality of survivorship in HNC patients.] Fibrosis and lymphedema secondary to the stromal response to [tissue damage from tumor or treatment are understudied and poorly understood mechanisms that contribute to late-effects of therapy.] We hypothesize [that late-effect fibrosis and lymphedema represent inter-related processes that exist on biological and clinical continuums. Further- more, recent data indicates that both] fibrosis and lymphedema may be associated [with chronic] inflammation resulting in [an active, ongoing process. Thus, lymphedema and fibrosis may: develop after treatment is completed; progress over time; and be self perpetuating]. The National Cancer Institute's strategic plan addresses the need to expand efforts to understand biologic, physical, psychological, and social mechanisms and their interactions that affect a cancer patient's response to disease, treatment, and recovery, and to support research on the biologic and physiological mechanisms involved in adverse chronic and late-effects of both current and new cancer treatment. The objective of this longitudinal, descriptive study is to investigate the fibrosis/ lymphedema continuum [in HNC patients]. Specific Aims are to: 1) determine prevalence and nature of late-effect (e 3 months post-treatment) fibrosis and/or lymphe- dema in HNC patients; 2) explore relationships among biological mechanisms of inflammatory response, genetic polymorphisms, [treatment factors], and late-effect fibrosis and/or lymphedema in HNC patients; and 3) [explore relationships among late-effect fibrosis and/or lymphedema and psychosocial stressors (depression and social withdrawal) in HNC patients. Data collection, using select repeated measures, will take place at end of treatment, six week intervals after treatment through 48 weeks post-treatment, and 15 and 18 month intervals post-treatment.] Nagin's group-based trajectory modeling will be used to evaluate our findings. If the aims are achieved and information is disseminated, important new information will be available to: 1) [serve as underpinnings for future studies in other cancer populations at high risk for development of fibrosis and/or lymphedema, such as those with breast, ovarian, prostate cancers, and melanoma; 2) aid in development of predictive risk models; 3) stimulate new avenues of preventive. interventional research (e.g. anti-inflammatory agents);] and 4) assist physicians and other healthcare professionals to better diagnose, reduce risk for, and treat late-effect fibrosis and/or lymphedema. PUBLIC HEALTH RELEVANCE: Head and neck cancer patients are living longer, and many suffer hardness and swelling in the head and neck post-treatment. We do not know why some experience these problems and others do not. This study will provide information so healthcare providers can better treat these patients.